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Pumped Up on Prozac

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Millions of people now rely on antidepressants, yet scientists still do not understand exactly how they work. Two recent studies hint at an answer: The drugs may provide a mood lift by growing and protecting neurons.

Prozac and its ilk quickly alter levels of chemicals such as serotonin in the brain, but they typically take weeks to ease depression symptoms. One theory holds that the drugs work by promoting the formation of neurons. As a test, neuroscientist René Hen at Columbia University and his colleagues treated mice with antidepressants but killed off any newly created neurons in the hippocampus, a brain region linked to learning and memory. Under those conditions, the antidepressants did not work. Hen speculates that changes in serotonin indirectly spur an increase in neurons in the hippocampus. If that is the key to fighting depression, drugs that directly promote neuron growth might be faster and less disruptive than existing medications, Hen says.

Brain imaging studies also show a link between the overall size of the hippocampus and recurrent bouts of major depression. Psychiatrist Yvette Sheline at Washington University and her colleagues recently found that patients who spent the most days depressed without medication had the smallest hippocampi. In this case, the change may be caused by a decrease in the connective branching between the neurons—a decrease that could be suppressed by antidepressants. “The more untreated depression you have, the more it’s harming your hippocampus,” Sheline says.